Functional Contribution and Targeted Migration of Group-2 Innate Lymphoid Cells in Inflammatory Lung Diseases: Being at the Right Place at the Right Time

Abstract

During the last decade, group-2 innate lymphoid cells (ILC2s) have been discovered and successfully established as crucial mediators of lung allergy, airway inflammation and fibrosis, thus affecting the pathogenesis and clinical course of many respiratory diseases, like for instance asthma, cystic fibrosis and chronic rhinosinusitis. As an important regulatory component in this context, the local pulmonary milieu at inflammatory tissue sites does not only determine the activation status of lung-infiltrating ILC2s, but also influences their motility and migratory behavior. In general, many data collected in recent murine and human studies argued against the former concept of a very strict tissue residency of innate lymphoid cells (ILCs) and instead pointed to a context-dependent homing capacity of peripheral blood ILC precursors and the inflammation-dependent capacity of specific ILC subsets for interorgan trafficking. In this review article, we provide a comprehensive overview of the so far described molecular mechanisms underlying the pulmonary migration of ILC2s and thereby the numeric regulation of local ILC2 pools at inflamed or fibrotic pulmonary tissue sites and discuss their potential to serve as innovative therapeutic targets in the treatment of inflammatory lung diseases.

Systemic immune response to vimentin and granuloma formation in a model of pulmonary sarcoidosis

“…Lung ILC2 cells are located close to the epithelial lining of large and small airways, and these cells were significantly enriched in the BAL fluid of vimentin-immunized mice. Although the absolute numbers of ILC2 are small, they are the early responders to lung inflammation and affect the clearing of pathogens and tissue repair [ 40 ]. Analysis of BAL from sarcoidosis patients for the presence of ILC2 will substantiate their role in disease pathogenesis.…”

Understanding immunity in a tissue‐centric context: Combining novel imaging methods and mathematics to extract new insights into function and dysfunction*

“…These imaging methods were also used to explore the state and function of innate lymphoid cells (ILC) in the gut and to determine that ILC2 are migratory, in contrast to the general view in the field 39,40 . This new insight into ILC2 biology has been confirmed and extended by others 41 …”

“…39,40 This new insight into ILC2 biology has been confirmed and extended by others. 41 Very recently, we have used multiplex imaging, together with IVM, to extend this concept of immune cell spatial polarization to the liver. Gola et al 42 found that the distribution of several immune populations, including Kupffer cells, CD8+ memory T cells, and NK T cells, all showed a higher density near the portal triad as compared to the central vein within a hepatic lobule.…”

Monitoring Group 2 Innate Lymphoid Cell Biology in Models of Lung Inflammation

“…Innate lymphoid cells (ILCs) are a heterogeneous population of lymphocytes that lack common lineage markers. ILCs are differentiated by their transcription factor expression profiles and cytokine production capabilities ( Wirtz et al, 2021 ). ILCs are categorized into three major subpopulations, ILC1s, ILC2s, and ILC3s, which are the innate counterparts to CD4 + Th1, Th2, and Th17 cells ( Artis and Spits, 2015 ).…”